Lupus erythematosus and lupus nephritis: symptoms

Symptoms of lupus nephritis are polymorphic and consist of a combination of various symptoms, some of which are specific for systemic lupus erythematosus.

• Increased body temperature (from subfebrile to high fever).
• Skin lesion: the most frequently observed erythema is a person in the form of a "butterfly", discoid rashes, but there are possible erythematous rashes of other localization, as well as more rare types of skin lesions (urticaria, hemorrhagic, papulonecrotic rashes, mesh or dendritic lyvedo with ulceration).

• The defeat of the joints is more often represented by polyartralgia and arthritis of the small joints of the hands, which are seldom accompanied by deformity of the joints.
• Polyserositis (pleurisy, pericarditis).
• Peripheral vasculitis: capillary tips of the fingers, rarely palms and soles, cheilitis (vasculitis around the red border of the lips), enanthema of the oral mucosa.
• The defeat of the lungs: fibrosing alveolitis, discoid atelectasis, high diaphragm standing, leading to the development of restrictive respiratory failure.
• CNS lesion: lupus cerebrovascular, most often manifested by intense headaches, convulsive seizures, mental disorders. Rare lesions of the nervous system include transverse myelitis, which has an unfavorable prognostic value.
• Defeat of the heart: more often myocarditis develops, less often the endocarditis of Liebman-Saks; it is also possible to damage the coronary vessels.
• Kidney damage: glomerulonephritis of varying severity.
• Trophic disorders: rapid weight loss, alopecia, nail damage.
• Lymphadenopathy.

[1], [2], [3], [4]

Pathomorphology of lupus erythematosus and lupus nephritis

The morphological picture of lupus nephritis is distinguished by significant polymorphism. Along with the histological changes characteristic of glomerulonephritis in general (proliferation of glomerulus cells, expansion of mesangium, changes in basilar membranes of capillaries, involvement of tubules and interstitium), specific morphological signs (fibrinoid necrosis of capillary loops, pathological changes of cellular nuclei (karyorexis and karyopicnosis), sharp focal thickening of the basal membranes of glomerular capillaries in the form of "wire loops", hyaline thromes would, hematoxylin bodies.

Immunohistochemical examination in glomeruli reveals IgG deposits, often in combination with IgM and IgA, as well as C3-components of complement and fibrin. At electron microscopic examination, deposits of immune complexes of different localization are found: subendothelial, subepithelial, intramembranous and mesangial. Pathognomonic signs of lupus nephritis are intra-endothelial virus-like inclusions in the glomerular capillaries that resemble paramyxoviruses.

In 50% of cases, in addition to glomerular, tubulointerstitial changes (in the form of dystrophy and atrophy of tubular epithelium, infiltration of interstitium by mononuclear cells, foci of sclerosis) are also noted. As a rule, the severity of tubulointerstitial changes corresponds to the severity of glomerular lesion; Isolated tubulointerstitial lesion occurs extremely rarely. In 20-25% of patients, small vessels of the kidneys are affected.

Clinical options for lupus nephritis

The modern clinical classification of lupus nephritis was proposed by I.E. Tareeva (1976). Depending on the severity of the symptoms of lupus nephritis, the nature of the course, the prognosis, there are several variants of lupus nephritis, in which various therapeutic approaches are needed.

• Active jade.
  • Rapidly progressive lupus nephritis.
  • Slowly progressive lupus nephritis:
    • with nephrotic syndrome;
    • with severe urinary syndrome.
• Inactive nephritis with minimal urinary syndrome or subclinical proteinuria.
• Symptoms of lupus nephritis depend on its morphological variant.
• Rapidly progressive lupus nephritis develops in 10-15% of patients.
  • According to the clinical picture, it corresponds to the classical subacute malignant glomerulonephritis and is characterized by a rapid increase in renal failure due to the activity of the kidney process, as well as nephrotic syndrome, erythrocytic activity and arterial hypertension, predominantly heavy current.
  • A feature of rapidly lupus nephritis is frequent (greater than 30% of patients) developing DIC syndrome clinically manifested bleeding (skin hemorrhagic syndrome, nasal, uterine, gastrointestinal bleeding) and thrombosis and having such laboratory signs as the emergence or growth of thrombocytopenia, anemia, reduction of fibrinogen in the blood, increased concentration of fibrin degradation products in the blood.
  • Often, rapidly progressive lupus nephritis is combined with heart and CNS lesions.
  • Morphologically, this option is more often associated with diffuse proliferative lupus nephritis (IV class), often with semilunar.
  • Isolation of this form of the disease is due to a severe prognosis, the similarity of the clinical picture to other rapidly progressive nephritis, the need to use the most active therapy.
• Active lupus nephritis with nephrotic syndrome develops in 30-40% of patients.

[5], [6], [7], [8], [9], [10]

Lupus Jade

Lupus nephritis is one of the most common causes of nephrotic syndrome in young women. The special features of lupus nephrotic syndrome include unusually very high proteinuria (such kind is observed, for example, renal amyloidosis) and, consequently, less severity hypoproteinemia and hypoalbuminemia, frequent combination with hypertension and hematuria, reduced tendency to recur than in chronic glomerulonephritis. Most patients report hypergammaglobulinemia, sometimes expressed, and, in contrast to patients with a different etiology of nephrotic syndrome, moderately elevated levels of a _2- globulin and cholesterol. Morphological examination usually reveals diffuse or focal proliferative lupus nephritis, less often - membranous (III, IV and V classes respectively).

• Active lupus nephritis with severe urinary syndrome, characterized by proteinuria from 0.5 to 3 g / day, erythrocytic,
  leukocyturia, is observed in about 30% of patients.
  • Hematuria is an important criterion for the activity of lupus nephritis. In most patients, a pronounced and persistent microhematuria is detected, usually in combination with proteinuria, and in 2-5% of cases, macrohematuria is noted. Isolated hematuria (hematuric nephritis) is rarely noted.
  • Leukocyturia can be a consequence of both the lupus proper process in the kidneys and the attachment of a secondary urinary tract infection. To differentiate these processes (to address the issue of timely early antibiotic therapy), it is advisable to explore the differential blood count, urine sediment: in case of aggravation of lupus nephritis show limfotsituriyu (lymphocytes for more than 20%), and secondary infection in the urinary sediment is dominated by neutrophils (80%) .
  • Arterial hypertension is noted in more than 50% of patients with this form of lupus nephritis.
  • The morphological picture is equally often represented by proliferative lupus nephritis and mesangial forms of the disease (classes II, III, IV).
  • If patients with rapidly progressive lupus nephritis and active lupus nephritis with nephrotic syndrome, the clinical picture is dominated by symptoms of renal disease, the patients with severe urinary syndrome to the fore extrarenal lesions (skin, joints, serous membranes, lungs).
• Lupus nephritis with minimal urinary syndrome is characterized by proteinuria of less than 0.5 g / day (subclinical proteinuria) without leukocyturia and, most importantly, without erythrocyturia. The disease proceeds with preservation of renal function in norm and without artheiral hypertension. The isolation of this type of jade is important for the choice of therapy; while the intensity of treatment is determined by the lesions of other organs. Morphological changes correspond to I or II class, although sometimes they are accompanied by tubulointerstitial and fibroplastic components.

Such clinical symptoms of lupus nephritis, such as renal failure and hypertension have a serious prognostic value.

• Renal failure is the main symptom of fast-progressive lupus nephritis. For the diagnosis, the growth rate of creatinine concentration in the blood is important: doubling the creatinine content in less than 3 months is a criterion for rapid progression. In a small part of patients with lupus nephritis (5-10%), acute renal failure is noted, which, in addition to high jade activity, may be due to the DIC syndrome, thrombotic microangiopathy of the intrarenal vessels in antiphospholipid syndrome (see "Kidney damage in antiphospholipid syndrome"), secondary infection, as well as renal medication as a result of antibiotic therapy. Unlike Bright Jade, in patients with systemic lupus erythematosus, the development of renal failure does not mean lack of disease activity even in the presence of clinical signs of uremia, and some patients need to continue immunosuppressive therapy after hemodialysis.
• Arterial hypertension occurs on average in 60-70% of patients with lupus nephritis. The frequency of development of arterial hypertension and the state of hemodynamics are closely related to the degree of nephritis activity (for example, in rapidly progressing nephritis, arterial hypertension is noted in 93% of patients, and for inactive - in 39%). The damaging effect of arterial hypertension on the kidneys, heart, brain and blood vessels in systemic lupus erythematosus is aggravated by autoimmune damage to these same target organs. Arterial hypertension worsens overall and renal survival, increases the risk of death from cardiovascular complications and the development of chronic renal failure. Normalization of arterial pressure when achieving remission of lupus nephritis also confirms the connection of arterial hypertension with lupus-nephritis with the severity of the activity of the process. Nephrosclerosis affects blood pressure only when it reaches significant levels. With moderate activity of lupus nephritis and systemic lupus erythematosus in general, an anti-phospholipid syndrome plays a special role as the cause of hypertension. The risk of developing "steroid" arterial hypertension in patients with systemic lupus erythematosus is 8-10%, and in the case of kidney damage - up to 20%. For the development of "steroid" arterial hypertension, not only the dose, but also the duration of treatment with glucocorticoids are important.

Classification of lupus erythematosus and lupus nephritis

Depending on the nature of the onset, the rate of progression of lupus erythematosus and lupus nephritis, the polysyndromicity of the process is affected by acute, subacute and chronic course of systemic lupus erythematosus (classification of VA Nasonova, 1972).

• In acute course, the disease begins suddenly with high fever, polyarthritis, serositis, skin rashes. Already in the onset of the disease or in the coming months, signs of damage to vital organs, mainly the kidneys and the central nervous system, are noted.
• With the most frequent, subacute, the disease develops more slowly, wavy. Viscerites do not appear simultaneously with lesions of the skin, joints, serous membranes. The characteristic polysyndromicity characteristic of systemic lupus erythematosus is formed within 2-3 years.
• Chronic course of the disease for a long time is manifested relapses of certain syndromes: articular, Reynaud, Verlhof; visceral lesions develop late.

Lupus nephritis is the most serious organ failure in systemic lupus erythematosus, found in 60% of adult patients and 80% of children, nevertheless the earliest symptom of lupus, along with arthralgia, skin lesions and serous membranes, lupus nephritis is only in 25% of patients, and among patients with a debut disease over the age of 50 years - less than 5%. The frequency of the onset of lupus nephritis depends on the nature of the course and activity of the disease: most often the kidneys are affected in acute and subacute flow and much less often - in chronic cases. Lupus nephritis, as a rule, develops in the first years after the onset of systemic lupus erythematosus, with high immunological activity, during one of the exacerbations of the disease. In rare cases, this renal involvement is the first symptom of lupus nephritis, preceding its extrarenal manifestations (the "nephritic" mask of systemic lupus erythematosus, which usually occurs with a nephrotic syndrome that can recur in some patients for several years before the development of systemic manifestations or signs of immunological activity of the disease ). The most acute and active forms of nephritis develop predominantly in young patients; in older people, the quieter course of both lupus nephritis and systemic lupus erythematosus is more often detected. As the duration of the disease increases, the incidence of lupus nephritis increases.

Symptoms of lupus nephritis are extremely diverse: from persistent minimal proteinuria, which does not affect the health of patients and practically does not affect the prognosis of the disease, to severe subacute (fast-progressive) nephritis with edema, anasarka, arterial hypertension and renal insufficiency. In 75% of patients, kidney damage develops on the background of an expanded clinical picture of the disease or in the presence of 1 or 2 symptoms (more often arthralgia, erythema or polyserositis). In such cases, it is sometimes the attachment of signs of kidney damage that allows a correct diagnosis to be made, despite the absence of any symptoms peculiar only to lupus nephropathy.

[11], [12], [13], [14], [15]

Morphological classification of lupus erythematosus and lupus nephritis

According to the morphological classification of domestic authors, the following forms of lupus nephritis are distinguished.

• Focal lupus proliferative nephritis.
• Diffuse lupus proliferative nephritis.
• Membranous.
• Mesangioproliferative.
• Mesangiocapillary.
• Fibroplasty.

The morphological classification of lupus nephritis, proposed by WHO in 1982 and approved in 2004 by the International Society of Nephrologists, which added to it and clarified, includes 6 classes of changes.

• I class - minimal mesangial lupus nephritis: with light microscopy, the glomeruli look normal, and in immuno-fluorescent - in mesangium, immune deposits are revealed.
• II class - mesangioproliferative lupus nephritis: with light microscopy, mesangial hypercellularity of different degree or expansion of the mesangial matrix is noted.
• III class - focal lupus nephritis: endocapillary or extracapillary glomerulonephritis, also involving mesangia, is detected in less than 50% of the glomeruli in active or inactive segmental (less than 50% of the vascular bundle) or global (lesion of more than 50% of the vascular bundle) with light microscopy.
• IV class - diffuse lupus nephritis: with light microscopy in more than 50% of the glomeruli, segmental or global endocapillary or extracapillary glomerulonephritis is identified, including necrotic changes, and mesangium involvement. With this form, subendothelial deposits are usually found.
• V class - membranous lupus nephritis is characterized by the presence of subepithelial immune deposits, detected by immunofluorescence or electron microscopy, and by a significant thickening of the capillary wall of the glomeruli.
• VI class - sclerosing lupus nephritis, in which more than 90% of the glomeruli are completely sclerotized.

When comparing the last 2 classifications, one can identify their similarity: the WHO class II class is close to mesangioproliferative glomerulonephritis according to the classification of V.V. Serov, V class according to WHO classification fully corresponds to membrane nephritis in the domestic classification, VI class - fibroplastic, nevertheless III and IV classes according to WHO classification are broader concepts than focal and diffuse lupus nephritis according to VV Serov classification, since include in addition to focal and diffuse proliferative lupus nephritis, a number of cases of mesangioproliferative and mesangiocapillary glomerulonephritis according to the domestic classification. Morphological type of the disease is the basis for choosing the optimal therapy for lupus nephritis.